Explain the timeline of tuberculosis therapy.

Use all four RIPE drugs – rifampin, isoniazid, pyrazinamide, and ethambutol – for two months and then just rifampin and isoniazid for the subsequent four months. (Think of the RIPE tubers: they were $4 for 2, but now they're $2 for 4!)

Most of the anti-mycobacterial drugs will induce resistance within a couple months. What is the big exception?

Isoniazid, which can be used to treat latent TB Think of the isoniazid ranger all alone by the man sleeping next to the cactus with middle-lobar granulomas.

Isoniazid works by ______________.

inhibiting mycolic acid production (like the pink cacti that are on the wall surrounding the town)

Isoniazid is activated by ________________.

catalase-peroxidase, also called catalase G (a fact represented by the cat with the G-shaped tail that is jumping over the wall and aggravating – activating – the isoniazid ranger)

How do bacteria gain resistance to isoniazid?

They downregulate catalase-peroxidase. Think of the cowboy who is silencing his bobcat so as not to alert the isoniazid burglar.

What's a good way to remember the adverse effects of isoniazid?

"INH Injures Nerves and Hepatocytes"

People who are ______________ are at increased risk for development of adverse effects from isoniazid.

slow acetylators (because INH is metabolized by acetylation) (Think of the guy with gloves and stockings – representing neuropathy – reaching for his acetylation gun but failing to get it in time.)

What side effect does pyridoxine prevent?

Neuropathy, seizures, and CNS toxicity Think of the bandit holding the pair of dice with 6 showing in an UNGLOVED hand.

Other than neuropathy and hepatotoxicity, what side effects can isoniazid cause?

Lupus (it is the I in HIPP-E) Metabolic acidosis (like the MUD PILE behind the wolf) Inhibition of CYP450

Rifampin has what side effects?

Induction of CYP450 (like the elevated, clean CYP bumper) Hepatotoxicity Orange discoloration of body fluids (like the orange beverage being spilled out of the rifampin carriage)

How does rifampin work?

It inhibits bacterial DNA-dependent RNA polymerase. (Think of the rifleman shooting the track switcher that's labeled DNA-RNA).

When is rifampin used as a monotherapy?

For close-contact meningitis caused by N. meningitis or H. influenzae

How does ethambutol work?

It inhibits arabinosyl transferase, thereby preventing carbohydrate polymerization at the cell wall. (Think of ETHyl the horse wrangler holding on to the ARABIan horse.)

Sketchy Pharm: Tuberculosis Drugs Flashcards by Billy Tran

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Sketchy Pharm: Tuberculosis Drugs Flashcards

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